Cancer is a serious threat in public health. The growth of malignant cancer is a serious challenge to a modern medical science due to its unique characteristics. These characteristics of cancer include uncontrolled cell proliferation causing loss of growth control exhibited by malignant tissues, capability for invading even local and distal tissues, unregulated cell differentiation, and often absence of effective treatment and prevention. Although cancer can develop in virtually any of the body's tissue at any stage, its etiology has not been completely explained. At present, a part of available major therapeutic methods are a surgery, radiotherapy and chemotherapy. The surgery often can be extreme means and cause serious results. The radiotherapy has an advantage of killing cancer cells, but this also damages non-cancer tissues simultaneously. The chemotherapy includes administering various anti-cancer drugs to a patient, but this often accompanies harmful side-effects. Globally, more than ten millions of people are diagnosed with cancer every year, and that number is predicted to increase to fifteen millions of new cases every year by 2020.
Of this chemotherapy, currently widely used three S phase of cell cycle-specific anti-cancer agents, 1-β-Darabinofuranosylcytosine (ara-C), camptothecin (CPT) and doxorubicin (DOX) are targeting three different enzymes (DNA polymerase α, topoisomerase I and II) (Abdel-Aziz W, et al., Biochem. Pharmacol., 68, pp 11-21, 2004). In some researches, topoisomerae I has been identified as a target molecule of camptothecin kind such as topotecan and irinotecan, etc (Hsiang Y H, et al., Cancer Res., 48, pp 1722-1726, 1988). Topoisomerase is classified to two kinds according to a cutting method of DNA strands. Type I topoisomerase (topoisomerase I) changes the status of DNA after making single-strand nick be formed in DNA substrates instantaneously, and Type II topoisomerase (topoisomerase II) changes the status of DNA after cutting all of DNA double-strands.
Furthermore, a vascular disrupting agent (VDA) is a drug which works in tumor vascular endothelial cells and decrease blood flow rate of a tumor blood vessels. Up to now many VDAs have been developed, but they are not developed for treating colorectal cancer or gastric cancer among cancers and there is not any drug having excellent effects on those cancers.
In addition, it is suggested that the efficacy of VDA can be significantly improved when it is administered by combining more than one therapy which has different mechanism from VDA in the aspect of coadministration, but until now there is no successful case. Therefore, the requirement for developing combination therapy and formulations composed of VDA and other therapy, thereby having relatively low toxicity and excellent effects on preventing or treating cancers such as colorectal cancer or ovarian cancer has been increased.